A pilot study is proposed to establish whether or not susceptibility to hepatotoxic injury is modified as a consequence of aging. This will be accomplished by comparing the effects of established hepatotoxins in male Fischer 344 rats at 4-5, 14-15 and 24-25 months of age. Liver injury will be evaluated from 1) alterations in components of hepatic microsomes, 2) elevations in serum activity of enzymes released from injured liver cells and 3) histomorphologic changes in liver sections. The hepatotoxic agents to be studied (allyl alcohol, bromobenzene, carbon tetrachloride and galactosamine) act by different mechanisms and produce damage at different sites. The study will provide background data for more extended research on how and why aging affects the response of the liver to noxious agents. Observations in the clinical literature suggest that the frequency of severe drug-induced liver disease increases with increasing age, and a long-term goal of this research is to understand how the elderly differ from young adults in their susceptibility of hepatotoxic drugs and environmental chemicals.